This is a request for four years of support to study 80 adolescent inpatients with Major Depressive Disorder (MDD). A random assignment, double-blind, placebo-controlled trial of Nortriptyline (NT) will be carried out over an 8-week period followed by a placebo withdrawal phase. Correlates of response to and relapse from NT treatment will be studied. Correlates to be studied include: Familial aggregation of psychopathology, neuroendocrine measures, monoamine measures, and associated clinical (non-depressive) symptoms. Correlations between different types of biological measures, and between biological measures and clinical and family measures will also be investigated.